Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)

• ClinicalTrials.gov Identifier: NCT03478462
• Recruitment Status: Recruiting
• First Posted: March 27, 2018
• Last Update Posted: December 2, 2021
• Sponsor: Cellectar Biosciences, Inc.
• Information provided by (Responsible Party): Cellectar Biosciences, Inc.

Tracking Information

• First Submitted Date: March 20, 2018
• First Posted Date: March 27, 2018
• Last Update Posted Date: December 2, 2021
• Actual Study Start Date: April 30, 2019
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2021)

Number of participants with dose limiting toxicities (DLT) [ Time Frame: up to 64 days ]

DLT will be assessed by physical examination, vital signs, and laboratory values

Original Primary Outcome Measures (submitted: March 26, 2018)

Number of participants with dose limiting toxicities (DLT) [ Time Frame: up to 85 days ]

DLT will be assessed by physical examination, vital signs, and laboratory values

Current Secondary Outcome Measures (submitted: March 16, 2021)

• Identification of recommended phase 2 dose of CLR 131 in children, adolescents, and young adults [ Time Frame: until non-tolerated dose is defined; dose escalation decision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion) ]
  Dose and regimen to be used in Phase 2 trials of CLR 131 in children, adolescents, and young adults
• Determination of preliminary antitumor activity of CLR 131 in children, adolescents, and young adults [ Time Frame: through Day 85 ]
  Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)
• Determination of therapeutic activity of CLR 131 in children, adolescents, and young adults [ Time Frame: up to 22 days post initial infusion ]
  Assessment via 131-I/CLR 131 SPECT/CT scans
• Determination of event free survival following CLR 131 infusion in children, adolescents, and young adults [ Time Frame: 1 month to 5 years ]
  Time from first infusion of CLR 131 until progression or recurrence of disease
• Determination of overall survival following CLR 131 infusion in children, adolescents, and young adults [ Time Frame: 1 month to 5 years ]
  Time from first infusion of CLR 131 until death due to any reason
• Determine dosimetry of CLR 131 in children, adolescents, and young adults [ Time Frame: up to 15 days post initial infusion ]
  Assessment of dosimetry via whole body planar imaging

Original Secondary Outcome Measures (submitted: March 26, 2018)

Determination of therapeutic activity of CLR 131 in children and adolescents [ Time Frame: through Day85 ]

Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures (submitted: March 26, 2018): Identification of recommended phase 2 dose of CLR 131 in children and adolescents [ Time Frame: until non-tolerated dose is defined; dose escalation decision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion) ]

Descriptive Information

• Brief Title: Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma
• Official Title: An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children, Adolescents, and Young Adults With Select Solid Tumors, Lymphoma, and Malignant Brain Tumors
• Brief Summary: The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.

Detailed Description

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Pediatric Solid Tumor
• Pediatric Lymphoma
• Pediatric Brain Tumor
• DIPG
• Neuroblastoma
• Ewing Sarcoma
• Rhabdomyosarcoma
• Osteosarcoma

Intervention

Drug: CLR 131

IV dose of CLR 131, increased/decreased by dose level; single or fractionated dose

Other Name: I-131-CLR1404

Study Arms

Experimental: CLR 131

CLR 131 intravenous administration

Intervention: Drug: CLR 131

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 26, 2018): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

All Patients

• Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g., neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain tumors that are clinically or radiographically suspected to be relapsed, refractory, or recurrent for which there are no standard treatment options with curative potential. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll without histological or cytological confirmation.
• ≥ 2 years of age and ≤ 25 years of age at time of consent/assent
• If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky performance status ≥ 60
• Platelets ≥ 75,000/µL (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
• Absolute neutrophil count ≥ 750/µL
• Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
• Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60 ml/min/1.73m2
• Alanine aminotransferase < 3 × ULN
• Bilirubin < 2 × ULN
• Patients who have undergone autologous or allogeneic bone marrow transplant must be at least 3 months from transplant.
• Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have availability or ability to collect an autologous hematopoietic stem cell back-up product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+ cells must be available.
• Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol.

Patients with Pediatric Solid Tumor or Lymphoma

• At least 1 measurable lesion with longest diameter of at least 10 mm. Patients with a lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron emission tomography (PET) positive may be enrolled at the investigator's discretion, even if not associated with a measurable lesion of at least 10 mm. Patients with neuroblastoma who have detectable disease may enroll provided they meet the requirements of the International Neuroblastoma Response Criteria.
• Patients with known brain metastases must have completed any radiotherapy or systemic treatments for brain metastases prior to enrollment; by investigator assessment be considered stable with no new signs or symptoms for at least 1 month, and on a stable dose of steroids (unchanged for three weeks prior to registration or on a steroid tapering regimen).

Patients with Recurrent or Refractory Brain Tumors

• At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging sequence.
• Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator's discretion.
• If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable.

Exclusion Criteria:

• Patients receiving active treatment for central nervous system metastases or those that are likely to require active treatment during anticipated participation in this trial. Patients with stable brain metastases treated with steroids may enroll at the investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless previously treated with surgery, systemic therapy, or radiotherapy with the patient neurologically stable. Patients with metastatic brain tumors that have been previously treated are allowed, provided the patient is neurologically stable (determined at the investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. For certain types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study]), at least 3 months must have elapsed. No washout is required for palliative focal radiation. NOTE: Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial
• Patients previously treated with iodine-131 (131I)-MIBG who have already received a cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in this trial, are not eligible.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Kate Oliver; 608-327-8125; clinical@cellectar.com

• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT03478462
• Other Study ID Numbers: DCL-17-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cellectar Biosciences, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Cellectar Biosciences, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jarrod Longcor; Cellectar Biosciences

• PRS Account: Cellectar Biosciences, Inc.
• Verification Date: November 2021